2023年 · 第136卷第23期

The cryopreservation of human oocytes and embryos is a key factor in assisted reproductive technology (ART). Based on the most recent guidelines and consensus^{[1,2,3,4,5,6,7,8]}and in combination with clinical practice, the Chinese Association of Reproductive Medicine has called on experts to summarize the technical process and details pertaining to the vitrification of human oocytes and embryos. The intention is to provide a set of comprehensive and systematic guidelines for vitrification and improve the quality of services offered at reproductive centers.

Epidermal growth factor receptor (EGFR) mutations are common oncogenic driver mutations in patients with non-small cell lung cancer (NSCLC). The application of EGFR-tyrosine kinase inhibitors (TKIs) is beneficial for patients with advanced and early-stage NSCLC. With the development of next-generation sequencing technology, numerous patients have been found to have more than one genetic mutation in addition to a single EGFR mutation; however, the efficacy of conventional EGFR-TKIs and the optimal treatments for such patients remain largely unknown. Thus, we review the incidence, prognosis, and current treatment regimens of EGFR compound mutations and EGFR concomitant mutations to provide treatment recommendations and guidance for patients with these mutations.

As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.

Cancer is a major threat to human health and causes death worldwide. Research on the role of radiotherapy (RT) in the treatment of cancer is progressing; however, RT not only causes fatal DNA damage to tumor cells, but also affects the interactions between tumor cells and different components of the tumor microenvironment (TME), including immune cells, fibroblasts, macrophages, extracellular matrix, and some soluble products. Some cancer cells can survive radiation and have shown strong resistance to radiation through interaction with the TME. Currently, the complex relationships between the tumor cells and cellular components that play major roles in various TMEs are poorly understood. This review explores the relationship between RT and cell-cell communication in the TME from the perspective of immunity and hypoxia and aims to identify new RT biomarkers and treatment methods in lung cancer to improve the current status of unstable RT effect and provide a theoretical basis for further lung cancer RT sensitization research in the future.

Inflammation is a major underlying mechanism in the progression of numerous cardiovascular diseases (CVDs). Regulatory T cells (Tregs) are typical immune regulatory cells with recognized immunosuppressive properties. Despite the immunosuppressive properties, researchers have acknowledged the significance of Tregs in maintaining tissue homeostasis and facilitating repair/regeneration. Previous studies unveiled the heterogeneity of Tregs in the heart and aorta, which expanded in CVDs with unique transcriptional phenotypes and reparative/regenerative function. This review briefly summarizes the functional principles of Tregs, also including the synergistic effect of Tregs and other immune cells in CVDs. We discriminate the roles and therapeutic potential of Tregs in CVDs such as atherosclerosis, hypertension, abdominal arterial aneurysm, pulmonary arterial hypertension, Kawasaki disease, myocarditis, myocardial infarction, and heart failure. Tregs not only exert anti-inflammatory effects but also actively promote myocardial regeneration and vascular repair, maintaining the stability of the local microenvironment. Given that the specific mechanism of Tregs functioning in CVDs remains unclear, we reviewed previous clinical and basic studies and the latest findings on the function and mechanism of Tregs in CVDs.

Patients with schizophrenia (SCZ) and major depressive disorder (MDD) share significant clinical overlap, although it remains unknown to what extent this overlap reflects shared neural profiles. To identify the shared and specific abnormalities in SCZ and MDD, we performed a whole-brain voxel-based meta-analysis using magnetization transfer imaging, a technique that characterizes the macromolecular structural integrity of brain tissue in terms of the magnetization transfer ratio (MTR).

A systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in PubMed, EMBASE, International Scientific Index (ISI) Web of Science, and MEDLINE for relevant studies up to March 2022. Two researchers independently screened the articles. Rigorous scrutiny and data extraction were performed for the studies that met the inclusion criteria. Voxel-wise meta-analyses were conducted using anisotropic effect size-signed differential mapping with a unified template. Meta-regression was used to explore the potential effects of demographic and clinical characteristics.

A total of 15 studies with 17 datasets describing 365 SCZ patients, 224 MDD patients, and 550 healthy controls (HCs) were identified. The conjunction analysis showed that both disorders shared higher MTR than HC in the left cerebellum (P=0.0006) and left fusiform gyrus (P=0.0004). Additionally, SCZ patients showed disorder-specific lower MTR in the anterior cingulate/paracingulate gyrus, right superior temporal gyrus, and right superior frontal gyrus, and higher MTR in the left thalamus, precuneus/cuneus, posterior cingulate gyrus, and paracentral lobule; and MDD patients showed higher MTR in the left middle occipital region. Meta-regression showed no statistical significance in either group.

The results revealed a structural neural basis shared between SCZ and MDD patients, emphasizing the importance of shared neural substrates across psychopathology. Meanwhile, distinct disease-specific characteristics could have implications for future differential diagnosis and targeted treatment.

There is limited data to comprehensively evaluate the epidemiological characteristics of multiple myeloma (MM) in China; therefore, this study determined the characteristics of the disease burden of MM at national and provincial levels in China.

The burden of MM, including incidence, mortality, prevalence, and disability-adjusted life years (DALYs), with a 95% uncertainty interval (UI), was determined in China following the general analytical strategy used in the Global Burden of Disease, Injuries, and Risk Factors Study 2019. The trends in the burden of MM from 1990 to 2019 were also evaluated.

There were an estimated 347.45 thousand DALYs with an age-standardized DALY rate of 17.05 (95% UI, 12.31-20.77) per 100,000 in 2019. The estimated number of incident case and deaths of MM were 18,793 and 13,421, with age-standardized incidence and mortality rates of 0.93 (95% UI, 0.67-1.15) and 0.67 (95% UI, 0.50-0.82) per 100,000, respectively. The age-specific DALY rates per 100,000 increased to more than 10.00 in the 40 to 44 years age group reaching a peak (93.82) in the 70 to 74 years age group. Males had a higher burden than females, with approximately 1.5- to 2.0-fold sex difference in age-specific DALY rates in all age groups. From 1990 to 2019, the DALYs of MM increased 134%, from 148,479 in 1990 to 347,453 in 2019.

The burden of MM has doubled over the last three decades, which highlights the need to establish effective disease prevention and control strategies at both the national and provincial levels.

The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis.

In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis.

A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP.

Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.

Type 2 diabetes mellitus (T2DM) is an independent risk factor for colorectal cancer (CRC), and the patients with CRC and T2DM have worse survival. The human gut microbiota (GM) is linked to the development of CRC and T2DM, respectively. However, the GM characteristics in patients with CRC and T2DM remain unclear.

We performed fecal metagenomic and targeted metabolomics studies on 36 samples from CRC patients with T2DM (DCRC group, n = 12), CRC patients without diabetes (CRC group, n = 12), and healthy controls (Health group, n = 12). We analyzed the fecal microbiomes, characterized the composition and function based on the metagenomics of DCRC patients, and detected the short-chain fatty acids (SCFAs) and bile acids (BAs) levels in all fecal samples. Finally, we performed a correlation analysis of the differential bacteria and metabolites between different groups.

Compared with the CRC group, LefSe analysis showed that there is a specific GM community in DCRC group, including an increased abundance of Eggerthella, Hungatella, Peptostreptococcus, and Parvimonas, and decreased Butyricicoccus, Lactobacillus, and Paraprevotella. The metabolomics analysis results revealed that the butyric acid level was lower but the deoxycholic acid and 12-keto-lithocholic acid levels were higher in the DCRC group than other groups (P < 0.05). The correlation analysis showed that the dominant bacterial abundance in the DCRC group (Parvimonas, Desulfurispora, Sebaldella, and Veillonellales, among others) was negatively correlated with butyric acid, hyodeoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid, cholic acid and glycocholate. However, the abundance of mostly inferior bacteria was positively correlated with these metabolic acid levels, including Faecalibacterium, Thermococci, and Cellulophaga.

Unique fecal microbiome signatures exist in CRC patients with T2DM compared to those with non-diabetic CRC. Alterations in GM composition and SCFAs and secondary BAs levels may promote CRC development.

Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient’s medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu’s Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion.

Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China’s guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test).

We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P<0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P<0.001). No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies.

The individualized red-cell transfusion strategy using the West-China-Liu’s Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries.

ClinicalTrials.gov, NCT01597232.

Human neutrophil lipocalin (HNL) has been used extensively to differentiate acute bacterial infection from febrile diseases as a biomarker to reflect the activation of the neutrophil. The serum HNL levels in the adult-onset Still’s disease (AOSD) patients with and without infection, as well as the healthy controls (HCs), were analyzed statistically in this study to evaluate the value of HNL for the diagnosis of AOSD.

A total of 129 AOSD patients were enrolled, from whom blood samples were drawn and the AOSD diagnosis was confirmed through the review of the medical records, where the systemic score, demographic characteristics, clinical manifestations, and laboratory parameters were also collected for the patients; in addition, a total of 40 HCs were recruited among the blood donors from the healthcare center with the relevant information collected. The HNL test was done for the blood samples with the enzyme-linked immunosorbent assay and the analyses were done for the correlations of HNL with clinical manifestations and diagnostic effectiveness.

The serum HNL increased significantly in the patients with only AOSD as compared with that in the HCs (139.76 ± 8.99 ng/mL vs. 55.92 ± 6.12 ng/mL; P < 0.001). The serum HNL level was correlated with the white blood cell (WBC) count (r = 0.335, P < 0.001), neutrophil count (r = 0.334, P < 0.001), erythrocyte sedimentation rate (r = 0.241, P = 0.022), C-reactive protein (r = 0.442, P < 0.0001), and systemic score (r = 0.343, P < 0.0001) in the AOSD patients significantly. Patients with fever, leukocytosis ≥15,000/mm³, and myalgia in the HNL-positive group were observed relatively more than those in the HNL-negative group (P = 0.009, P = 0.023, and P = 0.007, respectively). HNL was a more sensitive indicator than ferritin and C-reactive protein (CRP) to differentiate the AOSD patients with bacterial infection from AOSD-only patients, and the Youden index was 0.6 for HNL and 0.29 for CRP.

Serum HNL can be used as a biomarker for the diagnosis of the AOSD, and HNL is also observed to be associated with the disease activity.

To the Editor: Psoriasis is a common chronic immune-mediated systemic inflammatory disease^[1]characterized by irritating skin erythema, reduced quality of life, and associated systemic diseases including cardiovascular disease, diabetes, and metabolic syndrome. In 2017, 0.5% of China’s population was diagnosed with psoriasis.^[2]To improve the overall diagnosis and treatment level of psoriasis in China, the National Clinical Research Center for Skin and Immune Disease launched a national collaborative project called the Psoriasis Standardized Diagnosis and Treatment Center (also named Psoriasis Center) project,^[3]in which the first national real-world big data collection platform, Psoriasis Center Registry, was established with more than 300 medical centers across China by 2022. This study aimed to update the current general characteristics and treatment distribution of patients with psoriasis in China by describing the registry data at enrollment.

To the Editor:Introduction of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) has been highly efficacious in reducing the signs and symptoms of rheumatoid arthritis (RA) and in delaying or preventing structural joint damage. Furthermore, the development and clinical use of biological DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) have dramatically altered the prognosis of patients with RA, particularly when they are combined with a treat-to-target regimen (T2T).^[1]Consequently, over the last two decades, the rates of total hip arthroplasty (THA) and total knee arthroplasty (TKA) remained stable or even decreased in these special patient populations. Nevertheless, compared to patients with osteoarthritis, patients with RA have a higher risk of having worse functional outcomes and higher rates of complications after arthroplasty. This may be attributed to the complexity of the rheumatic disease process, including high disease activity, comorbidities, and immunosuppressive medications.^[2]A key to making perioperative medication management decisions is to balance the risk of periprosthetic infection with the risk of a disease flare.^[3]

To the Editor:New-onset headache within a week after craniotomy is commonly recognized as acute post-craniotomy headache (PCH). This headache pain mainly occurs within the first few post-operative days and is remarkably associated with a younger age, the female sex, and the retrosigmoid approach.^[1]The mechanisms of PCH mainly involve mechanical and chemical irritation and aseptic inflammation of the scalp muscles, periosteum of the skull, dura mater, and trigeminal nerves.^[2]The frequent onset of PCH leads to impaired daily activities, decreased quality of life, prolonged post-operative recovery, and worsened social functioning. The differential diagnosis of acute PCH may also lead to the patient receiving many unnecessary tests, including invasive tests such as a lumbar puncture.

To the Editor: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of various autoantibodies. Disease prevalence is 20 to 70 per 100,000 among adults, and 1.89 to 25.7 per 100,000 among children.^[1,2]The pathogenesis of SLE is associated with immune disorders, especially involving the activation of B and T cells, which can lead to abnormal antibodies with nuclear and cytosolic antigens from apoptotic cells of the immune complexes (ICs) removing the damaged cells, and excessive activation of the complement system, thus causing damage to target organs, such as the kidneys and lungs.^[3,4]

To the Editor:Systemic lupus erythematosus (SLE) is an autoimmune disease that tends to affect females of childbearing age. There are nearly 4 million people in China currently suffering from SLE, which can cause multiple organ damage in its early stages and seriously affect patients’ quality of life.^[1,2,3]Menstrual disorders are common in SLE patients and vary from heavy menstrual bleeding to amenorrhea. The etiology of menstrual irregularities includes the disease activity itself, glucocorticoids (GCs) treatment, and the use of some immunosuppressants.^[4]This multicenter, cross-sectional, web-based observational study investigated menstrual irregularity, pregnancy outcomes, and birth outcomes on SLE patients across China. The research was approved by the Ethics Committee of Peking University People’s Hospital, China (No. 2019PHB253-01). The patients were informed that consent was implied with completion of the questionnaire, and the process was anonymous and voluntary.

To the Editor:Acute kidney injury (AKI) is a frequent complication of both cardiac and major non-cardiac surgeries. Cardiopulmonary bypass (CPB)-assisted cardiac surgery was associated with a higher incidence of AKI than other surgeries without CPB, suggesting that CPB might be a risk factor for cardiac surgery-associated AKI (CSA-AKI).^[1]However, previous studies have demonstrated conflicting results regarding the association of CPB and CSA-AKI, as the diagnosis of AKI has been made according to different criteria.^[2,3,4,5]The most recent definition of AKI from an AKI Work Group, Kidney Disease: Improving Global Outcomes (KDIGO), allows for the determination of AKI based on a decline in the glomerular filtration rate (GFR) with subsequent increase in serum creatinine or a period of oliguria.^[6]We performed a retrospective cohort study to evaluate the association of CPB and postoperative AKI, using the KDIGO definition among patients undergoing on-pump or off-pump coronary artery bypass graft (CABG).

To the Editor: The latest variant of concern, Omicron, has become the dominant global variant immediately after it was first reported in November 2021.^[1]It contains >30 mutations in the spike protein, with 17 mutations in the receptor-binding domain, rendering it with increased transmissibility and capacity for immune evasion.^[1,2]Moreover, the waning of protection has been observed over time since the coronavirus disease 2019 (COVID-19) vaccination.^[3]Therefore, a booster is highly recommended. A large-scale study in the UK assessing the effectiveness of the booster vaccination with either the BNT162b2 or mRNA-1273 indicated that the booster shot substantially increased protection against symptomatic infection in patients with the confirmed Omicron variant infection.^[3]However, although the laboratory study has illustrated that the homologous booster with the inactivated COVID-19 vaccine could also yield potent neutralizing activity against the Omicron variant,^[4]clinical evidence regarding the effectiveness of this vaccination program is limited.

To the Editor:The classic case considered to be the primary application of the digital twin approach is the Apollo 13 mission in 1970. In 2003, the concept of the digital twin was presented by Prof. Michael Grieves at the University of Michigan. However, the widespread dissemination of the digital twin concept is attributed to the National Aeronautics and Space Administration’s application of digital twin for aerospace vehicle health maintenance and assurance in 2011.^[1]The improvement of new-generation information technology has led to a wider range of applications for digital twin technology, including healthcare.

To the Editor:Vitiligo is an autoimmune disease characterized by depigmented patches of skin and is challenging to manage with limited treatment options. Interferon (IFN)-γ-chemokine axis appears as a key driver of vitiligo. Melanocyte-specified CD8+ T cells produce IFN-γ when confront the melanocyte antigen, then activate Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in local keratinocytes, subsequently the keratinocytes produce the downstream chemokine C-X-C motif chemokine ligand 9 and 10 leading to additional recruitment of T cells to attack the melanocytes.